title: Insulin-like growth factor-II and insulin-like growth factor binding protein-2 prospectively predict longitudinal elevation of HDL-cholesterol in type 2 diabetes.
abstract: BACKGROUND
  Associations of insulin-like growth factor-II (IGF-II) and insulin-like growth factor binding protein-2 (IGFBP-2) with cardiovascular risk have been inadequately studied. We hypothesized that IGF-II and IGFBP-2 associate with longitudinal trends in lipid profiles in type 2 diabetes patients.
  
  
  METHODS
  Four hundred and eighty nine subjects with type 2 diabetes (age 27-87 years) from the Salford Diabetes Cohort were studied. Longitudinal clinical information was extracted for an eight-year period (2002-2009) from an integrated electronic dataset of primary care and hospital data.
  
  
  RESULTS
  There were 294 male subjects and mean age was 62.9 years. At baseline, IGF-II concentration was 602 ng/mL. HDL cholesterol at baseline was associated with log-IGF-II concentration in a model adjusted for age, gender, baseline body-mass index (BMI), estimated glomerular filtration rate (eGFR) and lipid-lowering therapy. IGFBP-1 and IGFBP-2 were associated with high HDL-cholesterol. A higher circulating IGF-II concentration at baseline was also associated with longitudinal increase in HDL-cholesterol in mixed-effects regression analyses independent of IGF-I, IGFBP-1, IGFBP-2, IGFBP-3, age, gender, eGFR, BMI and lipid-lowering therapy. Log-transformed baseline concentrations of IGFBP-1 and IGFBP-2 were also associated with longitudinal elevation in HDL-cholesterol. No association was observed for IGF-II or IGFBP-2 with longitudinal LDL cholesterol trends.
  
  
  CONCLUSIONS
  Our analyses based on 'real world' data demonstrate that higher baseline IGF-II and IGFBP-2 predict increased HDL concentration over time, implicating IGF-II in modulation of circulating HDL-cholesterol concentrations.
authors.affiliation: Vascular Research Group, The University of Manchester, Manchester, UK.
authors.forename: Ram P
authors.initials: RP
authors.lastname: Narayanan
authors.affiliation: School of Community Based Medicine, The University of Manchester, Manchester, UK.
authors.forename: Bo
authors.initials: B
authors.lastname: Fu
authors.affiliation: Vascular Research Group, The University of Manchester, Manchester, UK.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Oliver
authors.affiliation: Vascular Research Group, The University of Manchester, Manchester, UK.
authors.forename: Kirk W
authors.initials: KW
authors.lastname: Siddals
authors.affiliation: School of Community Based Medicine, The University of Manchester, Manchester, UK.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Donn
authors.affiliation: Vascular Research Group, The University of Manchester, Manchester, UK.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Hudson
authors.affiliation: Endocrinology and Diabetes, Faculty of Medical, Human and Life Sciences, The University of Manchester, Manchester, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: White
authors.affiliation: Department of Biochemistry, Leighton Hospital, Crewe, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Laing
authors.affiliation: Salford R&D, Salford Royal Hospital NHS Foundation Trust, Salford, UK.
authors.forename: William E R
authors.initials: WE
authors.lastname: Ollier
authors.affiliation: Vascular Research Group, The University of Manchester, Manchester, UK Department of Medicine, Leighton Hospital, Crewe, UK adrian.heald@mcht.nhs.uk.
authors.forename: Adrian H
authors.initials: AH
authors.lastname: Heald
authors.affiliation: Vascular Research Group, The University of Manchester, Manchester, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Gibson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D008076:Cholesterol, HDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged
chemical_list: D008076:Cholesterol, HDL; C035170:IGF2 protein, human; C577903:IGFBP2 protein, human; D018971:Insulin-Like Growth Factor Binding Protein 2; D007335:Insulin-Like Growth Factor II
keywords: HDL-cholesterol; Insulin-like growth factor-II; cholesterol; insulin-like growth factor binding protein-2; prospective; type 2 diabetes